early vs late dialysis

Bones can break, muscles can atrophy,
glands can loaf, even the brain can go to
sleep without immediate danger to
survival.
• But not!... should kidneys fail.... neither
bone, muscle, nor brain could carry on.
“Homer Smith”

Dr. Abrar Ali Katpar
Nephrology
KKH-Hail


Introduction.
3/18/2013
Dr. Abrar Ali Katpar@1st Nephrology
Symposium & Workshop on World
Kidney Day at KKH-Hail.
3


 Most critical decision to make along the course of
chronic renal insufficiency.
 Negative psychological impact on patients.
 Important socioeconomic implications.
 When to start - subject to much controversy.
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Initiation of dialysis.


 Free of uremic symptoms.
 To control volume overload, acid-base and
electrolyte disorders.
 And to provide a clearance of uremic toxins enough
to allow an adequate dietary protein and caloric
intake.
 When residual renal function fails to maintain all
these vital functions, we have a solid argument for
starting dialysis therapy.
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Goals of dialysis


K/DOQI
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GUIDELINE 1
When to Initiate Dialysis–Kt/Vurea Criterion (Opinion)
Unless certain conditions are met, patients should be advised to initiate some form of dialysis
when the weekly renal Kt/Vurea (Krt/Vurea) falls below 2.0. The conditions that may indicate
dialysis is not yet necessary even though the weekly Krt/Vurea is less than 2.0 are:
1. Stable or increased edema-free body weight. Supportive objective parameters for adequate
nutrition include a lean body mass >63%, subjective global assessment score indicative of
adequate nutrition and a serum albumin concentration in excess of the lower limit for the
lab, and stable or rising; and
2. Nutritional indications for the initiation of renal replacement therapy.
3. Complete absence of clinical signs or symptoms attributable to uremia.
A weekly Krt/Vurea of 2.0 approximates a kidney urea clearance of 7 mL/min and a kidney
creatinine clearance that varies between 9 to 14 mL/min/1.73 m2. Urea clearance should be
normalized to total body water (V) and creatinine clearance should be expressed per 1.73 m2 of
body surface area. The GFR, which is estimated by the arithmetic mean of the urea and
creatinine clearances, will be approximately 10.5 mL/min/1.73 m2 when the Krt/Vurea is
about 2.0.

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Early Start of Dialysis: A Critical Review
Steven Rosansky*, Richard J. Glassock†, William F. Clark‡
Abstract
Summary In the US, patients who initiate dialysis “early” (at Modification of Diet in
Renal Disease estimated GFR [eGFR]> 10 ml/min per 1.73m2) account for over 50
percent of new dialysis starts. This trend to an early start is based on conventional
wisdoms regarding benefits of dialytic clearance, that albumin levels are nutritional
markers, and early dialytic therapy is justified to improve nutrition especially in
diabetics and that waiting until low levels of eGFRmay be dangerous. In order to
justify early dialysis treatment, the therapy must provide a morbidity, mortality, or
quality of life benefit. The current review examines whether early dialysis initiation
provides any of these benefits and whether the conventional wisdoms that have
promoted this early dialysis trend are valid. Utilizing this information and the
results of recent large observational studies and the randomized controlled
Initiating Dialysis Early and Late (IDEAL) study, we suggest that dialysis initiation
is justified at GFR levels of 5–9 ml/min/1.73m2, if accompanied by uremia
symptoms or fluid management issues.


 Intractable ECV overload
 Hyperkalemia
 Metabolic acidosis
 Hyperphosphatemia
 Hypercalcemia or hypocalcemia
 Anemia
 Neurological dysfunction (eg, neuropathy, encephalopathy)
 Pleuritis or pericarditis
 Otherwise unexplained decline in functioning or well-being
 Gastrointestinal dysfunction (eg, nausea, vomiting, diarrhea,
gastroduodenitis)
 Weight loss or other evidence of malnutrition
 Hypertension.
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Complications That May Prompt Initiation of
Kidney Replacement Therapy.


 The key question is whether we have to start dialysis
prior to, or after the overt development of these
uremic signs and symptoms
1. The beneficial effects that dialysis can offer to the
pre-dialysis renal failure patient.
2. The potential complications of dialysis, and the
changes in the way of life that many patients have to
endure, are factors which should temper this
decision.
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When to Initiate??


 When to Initiate Dialysis : K t/V urea Criterion (Opinion)
patients should be advised to initiate some form of
dialysis when the weekly renal Kt/V urea < 2.0. Unless:
1. Stable or increased edema-free body weight.
2. No Nutritional indications
3. Complete absence of clinical signs or symptoms attributable
to uremia.
 A weekly Kt/V urea of 2.0 approximates a kidney urea
clearance of 7 mL/min and a kidney creatinine clearance
that varies between 9 to 14 mL/min/1.73 m 2.
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KDOQI.. Timing of Therapy


 patients with chronic kidney failure (e.g, GFR < 15 to
20 ml/min) who are not undergoing maintenance
dialysis, if protein-energy malnutrition (PEM)
develops or persists despite vigorous attempts to
optimize protein and energy intake and there is no
apparent cause for malnutrition other than low
nutrient intake, initiation of maintenance dialysis or
a renal transplant is recommended (Opinion).
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
 Timing of therapy: When patients reach stage 5 CKD
(estimated GFR < 15 mL/min/1.73 m2),
nephrologists should evaluate the benefits, risks, and
disadvantages of beginning kidney replacement
therapy. Particular clinical considerations and certain
characteristic complications of kidney failure may
prompt initiation of therapy before stage 5 (B)
 AJKD VOL 48, NO 1, SUPPL 1, JULY 2006
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Second update of the Clinical Practice Guidelines (CPGs) &
Clinical Practice Recommendations (CPRs)


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
Bonomini et al, 1985
 Reported that an early start of dialysis was
associated with reduced mortality & morbidity.
 Among a subset of patients who were subsequently
transplanted, there was a survival advantage for
those started dialysis early (n=50) vs later (n=96), as
well as less vascular calcification, bacterial
infection, dyslipidemia and hospitalization!
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Early initiation – Believers..


 CANUSA Study (McCusker et al 1996) PD
 Significantly poorer survival for patients with lower levels
of renal function when starting dialysis
 The mean creatinine clearance at the start of dialysis for all
patients was 38 L/wk (3.8 ml/min)
 12 and 24 month survival for those with creatinine clearance
<38 L/wk at start of dialysis was 82.1% and 73.6%,
respectively, compared with 94.7% and 90.8%, respectively,
for those with creatinine clearance >38 L/wk.
 In the CANUSA study, there was a survival advantage for
higher total (residual plus dialysis) Kt/V up to 2.0, and
possibly up to 2.3
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
 Tattersall et al. ( Am J Nephrol 15: 283 -2 89, 1995)
 Prospective cohort study of 63 patients in 1991–92.
 Demonstrated reduced survival in patients with less
residual renal function at start of dialysis, although
these patients were also significantly older and had
significantly more co-morbidity.
 Hospitalization length of stay was greater among
those with residual Kt/V <1.05 at time of initiation of
dialysis.
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
 Schulman G and Hakim RM
 Improving outcomes in chronic hemodialysis patients:
should dialysis be initiated earlier? Semin Dial 1996;
9(3):225-9
 patients initiated on dialysis with a creatinine
clearance > 10 ml/min had an 88% 10- year survival
when compared to 55% in those initiated at a
creatinine clearance of < 10 ml/min (mean 4 ml/min)
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
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Early initiation
However,
early initiation of dialysis expose
patients : complications of
dialysis, unnecessary lifestyle
restriction, potential increased
cost, patient fatigue.
No RCTs - Confounding influences
in other studies include referral
time bias, age, co-morbidity, patient
compliance and starting time bias.
Lead time bias.
Early initiation - skeptics - lead time bias
In the context of initiation of dialysis, lead-time bias refers to
the effect whereby measuring survival from the start of
dialysis increases apparent survival of those started with more
residual renal function i.e., earlier in the course of the
disease, than those who start dialysis with less residual renal
function
When to initiate dialysis: effect of proposed US guidelines on
survival.
Korevaar et al. Lancet 2001 Sep 29; 358(9287):1046-1050
In NECOSAD study (Korevaar et al.) estimated the effects of
lead-time bias on dialysis survival by using prediction
software based on the Finnish Cancer Registry
timely initiation - associated with a small survival benefit of 2.5
months
However, the extra time free of dialysis for “late starters ” was
only 4.1 months
This study suggested that any perceived survival benefit from
early start could be accounted for by lead-time
Early initiation - skeptics – QOL
(Korevaar et al 2002)
(Evaluation of DOQI guidelines: Early start of dialysis
treatment is not associated with better health-related
quality of life. Am J Kidney Dis 2002; 39:108- 1 15)
Prospective cohort study from Holland
38% of 237 incident dialysis patients commenced
dialysis late, as defined by the K/DOQI guidelines.
Compared with patients who have timely initiation,
the HRQOL among late starters was worse during the
first 6 months after initiation, but no different at 12
months
Early initiation does not prolong survival?
• Impact of timing of initiation of dialysis on mortality.
Beddhu et at. JASN 14: 2305-2312, 2003
• Post-hoc analysis of the MDRD study, comparing
early (predicted MDRD GFR>7.5 ml/min; N = 1,444)
with late (predicted GFR <7.5 ml/min); N =
1,476), higher MDRD GFR at initiation was associated
with an increased risk of death in multivariate Cox
model (hazard ratio 1.27 for each 5 ml/min increase)
• “ reflect an erroneous GFR estimation by MDRD
formula”
• Concluded that the data do not support early
initiation of dialysis
Early initiation of dialysis increases risk of mortality?
Kazmi et al – Am J Kidney Dis. 2005 Nov;46(5):887-96
undertook an evaluation of the impact of comorbidity
on the association between GFR at initiation and death
Results: greater GFR at initiation associated with a
greater risk for death in all populations
Patients in the general dialysis population who
initiated dialysis therapy at a GFR >10 mL/min/1.73
m2 had a 42% increased risk for death compared with
patients with a GFR < 5 mL/min/1.73 m2 at initiation
of dialysis therapy after adjusting for all covariates
Additional research required.


(IDEAL) TRIAL
The Initiating Dialysis Early and Late
 1. Enrollment, Randomization, and Follow-up.
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Definite answer?


The data for time to the initiation of dialysis (Panel A) were censored at the time of
death, transplantation, or withdrawal of consent or at the time a patient transferred to a
nonparticipating hospital, emigrated, or could not be contacted. The curves for time to death
(Panel B) are truncated at 7 years of follow-up and a cumulative hazard of 60%.
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2. Kaplan–Meier Curves for Time to the Initiation
of Dialysis and for Time to Death.


3/18/2013
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Primary and Secondary Outcomes, Including Adverse Events


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Effect of the Timing of Dialysis Initiation
in Subgroups
The forest plot shows the
hazard ratio (and 95%
confidence intervals) for
the primary outcome of
death from any cause,
with early initiation as
compared with late
initiation of dialysis,
according to each of the
prespecified subgroups.
The body-mass index
(BMI) is the weight in
kilograms divided by the
square of the height in
meters. GFR C–G denotes
glomerular filtration rate
estimated with the
Cockcroft–Gault equation,
and GFR MDRD the
glomerular filtration rate
estimated with the
Modification of Diet in
Renal Disease equation.


 Primary outcome = death from any cause.
 Secondary outcomes=
 cardiovascular events:
 cardiovascular death,
 nonfatal myocardial infarction,
 nonfatal stroke,
 transient ischemic attack,
 new-onset angina
 infectious events:
 death or hospitalization due to any infection-related cause,
 complications of dialysis :
 temporary placement of an access catheter,
 need for access revision,
 infection at the access site,
 fluid and electrolyte disorders requiring hospitalization,
 additional dialysis.
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Study Outcomes


3/18/2013
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When to initiate dialysis?
Rosansky and colleagues[1] addresses the issue
of when is the appropriate time to start dialysis.
This study raises questions about the increasingly
common practice of an early start to dialysis.
The title of the paper appropriately is "Early Start of
Hemodialysis May Be Harmful."
The higher the GFR at the time dialysis was
started, the higher the subsequent mortality and, in this
study, first year mortality. Patients who started dialysis
with GFRs in the 5-10 mL/min range had substantially
lower mortality than those who started dialysis at each
successively higher level of GFR, including 10-15 mL/min
and over 15 mL/min.


Adhere to best practice…….
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 AJKD VOL 48, NO 1, SUPPL 1, JULY 2006.
 http://www.kidney.org/professionals/kdoqi/guid
elines_commentaries.cfm
 http://ebookee.org/Nephrology-eBook-
Pack_1066049.html
 http://www.expertconsultbook.com
 http://patientsafetyauthority.org/ADVISORIES
 https://www.nephropath.com
 http://kidney.niddk.nih.gov/kudiseases/pubs/he
modialysisdose
 http://www.medscape.org
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References


Thank you
3/18/2013
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early vs late dialysis

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